Short chain fatty acids (SCFAs) are the main products of dietary fibers that are not digested by the human body, and they have been shown to affect human metabolism and inflammation. The amount of SCFAs in the body is related to many human diseases, and studies have focused on elucidating their roles and target molecules in both metabolic and immune responses. Thus, the quantitation of SCFAs in biological samples becomes crucial in understanding their important roles in the human body. Herein, a facile profiling method of SCFAs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and then applied to biological samples. C2-C6 SCFAs were derivatized while using 4-acetamido-7-mercapto-2,1,3-benzoxadiazole for 5 min. at room temperature prior to LC-MS/MS analysis, and characteristic fragmentation patterns and increased hydrophobicity after chemical derivatization enabled specific discrimination among 12 SCFAs. Derivatization was fast and reliable, and the reaction products were stable for a week at 4 °C. The developed method was applied to measure SCFAs in mouse feces, plasma, and human exhaled breath condensates. This fast and simple method can save labor and effort to profile SCFAs from various biological samples.

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by excessive collagen matrix deposition and extracellular remodeling. Signaling pathways mediated by fibrotic cytokine transforming growth factor β1 (TGF-β1) make important contributions to pulmonary fibrosis, but it remains unclear how TGF-β1 alters metabolism and modulates the activation and differentiation of pulmonary fibroblasts. We found that TGF-β1 lowers NADH and NADH/NAD levels, possibly due to changes in the TCA cycle, resulting in reductions in the ATP level and oxidative phosphorylation in pulmonary fibroblasts. In addition, we showed that butyrate (C4), a short chain fatty acid (SCFA), exhibits potent antifibrotic activity by inhibiting expression of fibrosis markers. Butyrate treatment inhibited mitochondrial elongation in TGF-β1-treated lung fibroblasts and increased the mitochondrial membrane potential (MMP). Consistent with the mitochondrial observations, butyrate significantly increased ADP, ATP, NADH, and NADH/NAD levels in TGF-β1-treated pulmonary fibroblasts. Collectively, our findings indicate that TGF-β1 induces changes in mitochondrial dynamics and energy metabolism during myofibroblast differentiation, and that these changes can be modulated by butyrate, which enhances mitochondrial function.

The n-3 fatty acid (FA) has evoked considerable interest as a modifiable factor for maintenance of muscle health owing to its anti-inflammatory properties. To clarify this possibility, we investigated circulating n-3 FA level, a reliable biomarker of FA status in the body, in relation to sarcopenia in a cohort of Asian older adults. Blood samples were collected from 125 participants who underwent comprehensive assessment of muscle mass and function. Serum FA level was measured by gas chromatography/mass spectrometry. Sarcopenia was diagnosed using the cut-off points specified for the Asian population. After adjusting for sex, age, and body mass index, subjects with sarcopenia and those with low muscle strength had 36.5% and 32.4% lower serum n-3 levels (P = 0.040 and 0.030), respectively, than controls. The odds ratios per standard deviation increment in serum n-3 level for sarcopenia and low muscle strength were 0.29 and 0.40 (P = 0.015 and 0.028), respectively. A higher serum n-3 level was significantly associated with greater muscle strength (P = 0.038). These findings suggest a possible protective effect of n-3 FA on human muscle homeostasis. Further well-designed large-scale longitudinal studies are necessary to understand the definite role of circulating n-3 FA level in sarcopenia risk assessment.

Kim GT, et al. J Lipid Atheroscler. 2020 May;9(2):291-303. https://doi.org/10.12997/jla.2020.9.2.291